Rheumatoid Arthritis Clinical Trial
Official title:
Genetics of Rheumatoid Arthritis: The North American Rheumatoid Arthritis Consortium
This study attempts to identify the genes responsible for rheumatoid arthritis (RA), or
inflammation of the joints. It is known that genes play an important role in RA, but their
number and significance have not been determined. RA tends to run in families. This study
will examine the DNA (hereditary material) of patients with RA and their family members to
try to determine which chromosomes(s) contain the genes responsible for the disease.
Patients with rheumatoid arthritis and their family members may be eligible for this study.
Participants with RA who have a brother or sister with RA will undergo the following
procedures:
- Review of their medical records
- Medical history
- Examination of the joints
- Hand X-rays
- Blood tests
Participants who 1) do not have RA but who have a relative with the disease, or 2) have RA
and a relative other than a brother or sister who has the disease will provide a blood sample
or a buccal (cheek) cell sample. Cheek cells are obtained by swishing a small amount of
mouthwash in the mouth or by lightly bushing the inside of the cheek with a swab or brush.
The samples will be tested for rheumatoid factor, DNA studies, and HLA type (a blood type
found on white blood cells). Certain HLA types have been associated with an increased risk or
severity of RA.
The purpose of this protocol is to identify genetic susceptibility loci for rheumatoid
arthritis. The Genetics and Genomics Branch of the Intramural Research Program of NIAMS [now
the
Inflammatory Diseases Section of the Intramural Research Program of NHGRI] has joined with
several extramural centers to form the North American Rheumatoid Arthritis Consortium
(NARAC). The Consortium intends to identify and obtain clinical specimens on a total of 1000
sibling pairs with rheumatoid arthritis; up to 100 sibling pairs will be recruited at the
Clinical
Center. Samples from parents and other family members will also be obtained, where
appropriate. Rheumatoid factors, HLA-DR typings, and hand films will be obtained on all
sibling pairs. In addition, DNA will be extracted from peripheral blood or buccal scrapings.
The
DNA from all 1000 sibling pairs will be typed for a set of approximately 350 genetic markers
in
order to identify chromosomal regions likely to harbor genes conferring susceptibility to
rheumatoid arthritis. For those chromosomal regions that are positive in this initial screen,
families will be genotyped for additional markers to define disease-associated haplotypes,
and high density single nucleotide polymorphism (SNP) analysis will be conducted to narrow
the regions of interest. Candidate genes will be chosen from the narrowed regions of
interest, and/or based on functional considerations, and will be screened for mutations in
rheumatoid arthritis.
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